Method of making 8-hydroxy quinoline



Patented Nov. 29, 1949 METHOD OF MAKING 8-HYDROXY- QUIN tion of NewJersey OLINE Nathaniel Grier, Brooklyn, N. Y., and Charles Casalbore,Passaic, N. J., assignors to Dar-Syn Laboratories, Inc., Hawthorne, N. Ja corpora- No Drawing. Application January 7, 1948, Serial No. 1,068

14 Claims.

The present invention is directed to the manufacture of 8-hydroxyquinoline and more particularly to an improved process resulting in ahigh yield of the product.

S-hydroxy quinoline is of considerable value in industry as a raw orintermediate material for the manufacture of derivatives thereof and forvarious other purposes. A number .of methods for its production havebeen proposed and used but none of them has been completelysatisfactory. For instance, one method involved the reaction ofo-nitrophenol or o-aminophenol with glycerine. This process was veryineflicient and maximum yields of 30 to 40% based on the initialingredients were obtained. The reactants were relatively expensive, andin view of the unsatisfactory yield, this process is of limited use.

Other proposed processes involved the reaction of 8-chloro-quinolinewith ammonia, followed by a sulphuric acid treatment. Another processconsisted in the demethylation of B-methoxyquinoline. While the yieldsof the B-hydroxy quinoline were more satisfactory than in the abovementioned process, the overall yield was extremely low because thestarting materials are obtainable only in poor yield.

Still another process which has been found of some use in industryinvolves the reaction of quinoline-8-sulfonicacid with sodium hydroxide.The starting material was mixed with the sodium hydroxide and a verysubstantial amount of water whereby solution of the sodium hydroxidetook place and the reaction mixture was heated until the mass becamefused. This required a considerable length of time and after thereaction was complete, the molten material was allowed to solidifyandwas broken up physically. It was then dissolved in hydrochloric acid andthe 8- hydroxy quinoline was steam distilled to purify the same. Thetemperature of the fusion and reaction was probably between 190 and 200C. While it was claimed that a 50% yield was obtainable thereby, actualexperience shows that the yields were only from 20 to 30%. In an attemptto improve this process, a procedure was su M gested in which theoperation took place in an autoclave under pressure and the resultantliquid slurry was maintained at 220 to 230 C. for three hours at apressure of 17 to 18 atmospheres. This method was quite burdensome anddiflicult to operate, particularly on a relatively large commercialscale and experience has shown that the yield of 8-hydroxy quinoline wasnot more than about 50% The present invention utilizes a process whereinquinoline 8-sulfonic acid, or its alkali metal or alkaline earth metalsalts, is reacted with sodium hydroxide, it being among the objects ofthe present invention to provide a process wherein the reaction takesplace in the semi-solid phasewithout fusion of the constituents.

It is also among the objects of the present invention to provide aprocess wherein a relatively high temperature is maintained for arelatively short time whereby a highly eilicient operation is obtained.

It is still further among the objects of the present invention toprovide a process which is of simple character, does not require the useof high pressure and may be operated by relatively un skilled labor withresulting very high yields of 8-hydroxy quinoline.

In the practice of the present invention, there is provided a mixture ofsodium hydroxide in divided form, for instance, in the form of flakes,powder or pellets. The proportion or ratio of the sodium hydroxide tothe quinoline 8-sulfonic acid is relatively critical and the amount ofsaid hydroxide by weight is 1.2 to 2 parts for each part of thequinoline 8-sulfonic acid. If a lesser proportion of the hydroxide isused, it becomes difllcult to completely convert the quinoline8-sulfonic acid and if a higher amount of the alkali is used, the yieldsare reduced.

The reaction mixture includes a very small amount of water. The water ispresent in not over 4% based on theflsodium hydroxide present andpreferably between .5% and 4% of water is used. It has been found thatthe ratio of sodium hydroxide to water by weight should be 35 to partsof sodium hydroxide to one part of water for the best results. Thisratio is suflicient so that at the temperature of reaction, the sodiumhydroxide is in the semi-solid phase and the reaction is asemi-solid-solid type of reaction.

Usually the operation is conducted in an open vessel or in a ventedvessel to avoid superatmospheric pressure as it has been determined thathigh pressures are unnecessary for the reaction under the presentconditions. The temperatures used range from 250 C. up to about 290 C.The reaction starts slowly at about 250 C. and reaches a maximum atabout 290 C. If lower temperatures 'are used, the reaction is so slow asto practically not take place, while if the temperature is raised tosubstantially above 290 C., the yield of I 8-hydroxy quinoline isreduced to a substantial extent depending on the temperature used.

Only a short time is required for the operation and the mixture ismaintained at the reaction temperature for not over thirty minutes andusually between five and thirty minutes. In most operations, from sevento ten minutes has been found eminently satisfactory to -give effectiveresults. In conducting the reaction the .alkali metal hydroxide and thewater are first heated to the reaction temperature, the mixture isstirred or agitated continuously and the quinoline 8- sulfonic acid orits aforesaid salts is added into the mixture in a very short time whilecontinuing the agitation. In a few minutes, the reaction is complete andthe product may be treated in any well-known manner to recover the pure8-hydroxy quinoline.

The following is a specific example of one method of operation of thepresent invention.

The reaction vessel may be an open kettle placed under a hood or aclosed vessel provided with an exit pipe for gases. There is introducedinto the reaction vessel 335 parts by weight of flake sodium hydroxideand 8.4 parts by weight of water and the mixture is heated to 270 C. Thevessel is provided with a mechanical stirrer and the mixture is stirredvigorously while adding thereto 210 parts by weight of powderedquinoline 8-sulfonic acid. The molecular ratio of sodium hydroxide toquinoline 8-sulfonic acid is 8.35 to 1. The stirring is continued afterthe addition of the quinoline 8-sulfonic acid, whereby the sodium saltof quinoline 8-sulfonic acid which is formed in the initial stages ofthe reaction is gradually converted into a light yellow salt of8-hydroxy quinoline. The reaction takes approximately ten minutes andthe completeness thereof is gauged by the light yellow color of the to73 C. and the yield is about 132 parts by weight or 91% based on thestarting material.

There are numerous advantages inherent in the present process, includingthe fact that the reaction being in the semi-solid state is more readilycontrolled and a high temperature of reaction for a short time avoidsthe possibility of the formation of decomposition products which have inthe past been formed at lower temperatures and longer times of reaction.The yield in every case is very high and yields of 95 and 96% are notuncommon. Because of the speed of the reaction and the lack of necessityof close control of conditions, the operation becomes simple and arelatively small amount of equipment is capable of producing relativelylarge yields.

Although the invention has been described setting forth a singlespecific embodiment thereof, such example does not limit the inventionbut is intended to illustrate the character thereof. Many variations inthe details may be made within the spirit of the invention, as forexample, alkali metal or alkaline earth metal salts may replace the freequinoline-B-sulfonic acid. The solution of the product may be in someother acid than sulphuric, such as hydrochloric acid solution. Alsoinstead of allowing the reaction prodnot to cool before dissolving it inthe acid for the refining operation, the hot reaction product may beintroduced into the dilute aqueous acid with good results. If the highertemperatures of reaction are used, the time of reaction is corre-'spondingly less within the limits set forth above.

The reaction product, while still at or near the reaction temperature,may be dissolved in water, thus freeing the sodium salt of B-hydroxyquinoline from the excess of sodium hydroxide, by precipitation from thesodium hydroxide solution. After separation of the salt, the sodiumhydroxide in the solution may be recovered for re-use.

The process may also be altered whereby the mixture of the quinoline8-sulfonic acid, sodium hydroxide and water is first made in the coldand the mixture is passed rapidly through a heated reaction vessel,heated at such a rate as to bring the temperature up to above 250 C. ina very few minutes. The mixture is held at said temperature for a fewminutes in order to complete the reaction and the product may then beutilized in any suitable manner. It is also possible to operate thereaction in a continuous manner by making a mixture of sodium hydroxideand water, passing the same continuous through a heated tube or troughfitted with a screw conveyor and at a desired point during the passageof the alkali through the reaction vessel, where the temperature hasbeen raised to the proper point, the powdered quinoline-8-sulfonio acid,or its aforesaid salts, is introduced and. is carried along by thealkali. Simultaneouslf the operation of the screw conveyor thoroughlyand uniformly mixes the constituents together and the reaction goes tocompletion in a short time.

These and other changes in the details of the invention may be madewithin the principles herein set forth and the invention is therefore tobe broadly construed and not to be limited except by the character ofthe claims appended hereto.

We claim:

1. A method which comprises providing divided sodium hydroxide, addingthereto 0.5 to 4% of water, heating said mixture to a temperature of 250C. to 290 C., introducing a compound taken from the group consisting ofquinoline-E-sulfonic acid and its alkali and alkaline'earth metal saltsinto said mixture, the ratio of sodium hydroxide to said sulphonic acidbeing 12-2 to 1, and agitat ing the same, whereby the sodium salt of8-hy droxy quinoline is formed.

2. A method of making 8-hydroxy quinoline which comprises providingdivided sodium hydroxide, adding thereto 0.5 to 4% of water, heatingsaid mixture to a temperature of 250 C. to 290 C., introducing acompound taken from the group consisting of quino1ine-8-sulfonic acidand its alkali and alkaline earth metal salts into said mixture, theratio of sodium hydroxide to said sulphonic acid being 1.2-2 to 1,agitating the same, whereby the sodium salt of 8-hydroxy quinoline isformed, and dissolving the product in dilute mineral acid to form8-hydroxy quinoline.

3. A method of making B-hydroxy quinoline which comprises providingdivided sodium hydroxide, adding thereto 0.5 to 4% of water, heatingsaid mixture to a temperature of 250 C. to 290 C., introducing acompound taken from the group consisting of quinoline-8-sulfonic acidand its alkali and alkaline earth metal salts into said mixture, theratio of sodium hydroxide to said sulphonic acid being 1.2-2 to 1. aitating the same,

o whereby the sodium salt of B-hydroxy quinoline is formed, dissolvingthe product in dilute mineral acid to form 8-hydroxy quinoline, andsteam distilling said 8-hydroxy quinoline.

4. A method of making 8-hydroxy quinoline which comprises providingdivided sodium hydroxide, adding thereto 0.5 to 4% of water, heatingsaid mixture to a temperature of 250 C. to 290 C., introducing acompound taken from the group consisting of quinoline-8-sulfonic acidand its alkali and alkaline earth metal salts into said mixture, theratio of sodium hydroxide to said sulphonic acid being 1.2-2 to 1,agitating the same, whereby the sodium salt of 8-hydroxy quinoline isformed, and dissolving the product in dilute mineral acid while atapproximately the reaction temperature to form 8-hydroxy quinoline.

5. A method which comprises providing divided sodium hydroxide, addingthereto 0.5 to 4% of water, heating said mixture to a temperature of250-290 C. without fusion, introducing a compound taken from the groupconsisting of quinoline-8-sulfonic acid and its alkali and alkalineearth metal salts into said mixture, the ratio of sodium hydroxide tosaid sulphonic acid being 12-2 to 1, and agitating the same, whereby,the sodium salt of 8-hydroxy quinoline is formed.

6. A method which comprises providing divided sodium hydroxide, addingthereto 0.5 to 4% of water, heating said mixture to a temperature of 250C. to 290 C., introducing a compound taken from the group consisting ofquinoline- 8-sulfonic acid and its alkali and alkaline earth metal saltsinto said mixture after it has reached said temperature, the ratio ofsodium hydroxide-to said sulphonic acid being 12-2 to 1, and agitatingthe same, whereby the sodium salt of B-hydroxy quinoline is formed.

'1. A method which comprises providing. divided sodium hydroxide, addingthereto 0.5 to 4% of water and in the proportion of 1 to 35-45 parts byweight of the sodium hydroxide, heating said mixture to a temperature of250 C. to 290 C., introducing a compound taken from the group consistingof quinoline-8-sulfonic acid and its alkali and alkaline earthmetalsalts into said mixture, the ratio of sodium hydroxide to said sulphonicacid being 12-2 to 1, and agitating the same, whereby the sodium salt of8-hydroxy quinoline is formed.

8. A method which comprises providing divided sodium hydroxide, addingthereto 0.5 to 4% of water, heating said mixture to a temperature of 250C. to 290 C., introducing a compound taken from the group consisting ofquinoline-8-sulfonic acid and its alkali and alkaline earth metal saltsinto said mixture, the ratio of sodium hydroxide to said sulphonic acidbeing 1.2-2 to 1, and agitating the same. te ratio of sodium hydroxideto quinoline-B-sulfonic acid by weight being 12-2 to 1, whereby thesodium salt of 8-hydroxy quinoline is formed.

9. A method which comprises providing divided sodium hydroxide, addingthereto 0.5 to 4% of water, heating said mixture to a temperature of 250C. to 290 C., introducing a compound taken lrom the group consisting ofquinoline-B-sulfonic acid and its alkali and alkaline earth metal saltsinto said mixture, the ration of sodium hydroxide to said sulphonic acidbeing 12-2 to 1, and agitating the same. maintaining the reactiontemperature for from 5 to 30 minutes, whereby the sodium salt ofB-hydroxy quinoline is formed.

10. A method which comprises providing divided sodium hydroxide, addingthereto 0.5 to 4%- of water, heating said mixture to a temperature ofabout 270 C., introducing a compound taken from the group consisting ofquinoline-B-sulfonic acid and its alkali and alkaline earth metal saltsinto said mixture, the ratio of sodium hydroxide to said sulphonic acidbeing 12-2 to 1, and agitating the same, maintaining the reactiontemperature for about 7 to 10 minutes, whereby the sodium salt of8-hydroxy quinoline is formed.

11. A method which comprises providing divided sodium hydroxide, addingthereto 0.5 to 4% of water, heating said mixture to a temperature of 250C. to 290 C., introducing a compound taken from the group consisting ofquinoline-8-sulfonic acid and its alkali and alkaline earth metal saltsinto said mixture, the ratio of sodium hydroxide to said sulphonic acidbeing 12-2 to 1, and agitating the same while maintaining the reactantsin the semi-solid state, whereby the sodium salt of. B-hydroxy quinolineis formed.

12. A method which comprises providing divided sodium hydroxide, addingthereto 0.5 to 4% of water, advancing said mixture continuously whileheating said mixture to a temperature of 250 C. to 290 C. introducing acompound taken from the group consisting of quinoline-8-suli'onic acidand its alkali and alkaline earth metal salts into said mixturecontinuously at a point in the travel of said mixture where a reactiontemperature exists while continuously agitating the same, the ratio ofsodium hydroxide to said sulphonic acid being 12-2 to 1, whereby thesodium salt of 8-hydroxy quinoline is formed.

13. A method which comprises providing divided sodium hydroxide, addingthereto 0.5 to 4% of water, introducinga compound taken from the groupconsisting of quinoline-8-sulfonic acid and its alkali and alkalineearth metal salts into said mixture, the ratio of sodium hydroxide tosaid sulphonic acid being 12-2 to 1, then rapidly heating the same to atemperature of 250 C. to 290 C., while agitating, whereby the sodiumsalt of 8-hydroxy quinoline is formed.

14. A method which comprises providing divided sodium hydroxide, addingthereto 0.5 to 4% of water, heating said mixture to a temperature of 250C. to 290 C., introducing a compound taken from the group consisting ofquinoline-8- sulfonic acid and its alkali and alkaline earth metal saltsinto said mixture, the ratio of sodium hydroxide to said sulphonic acidbeing 12-2 to 1, and agitating the same, whereby the sodium salt of8-hydroxy quinoline is formed, dissolving the reaction product while atreaction temperature in water, whereby said sodium salt is freed fromthe excess of sodium hydroxide.

NATHANIEL GRIER. CHARLES CASALBORE.

REFERENCES CITED The following references are of record in the flle ofthis patent:

UNITED STATES PATENTS Name Date Fischer Jan. 2. 1883 Number

